The term vaccine derives from Edward Jenner's 1796 use of the term cow pox (Latin variolæ vaccinæ, adapted from the Latin vaccīn-us, from vacca cow), which, when administered to humans, provided them protection against smallpox.
The 20th century saw the introduction of several successful vaccines, including those against diphtheria, measles, mumps, and rubella. Major achievements included the development of the polio vaccine in the 1950s and the eradication of smallpox during the 1960s and 1970s. Maurice Hilleman was the most prolific of the developers of the vaccines in the twentieth century. As vaccines became more common, many people began taking them for granted. However, vaccines remain elusive for many important diseases, including malaria and HIV. Vaccines may be dead or inactivated organisms or purified products derived from them.
There are several types of vaccines currently in use. These represent different strategies used to try to reduce risk of illness, while retaining the ability to induce a beneficial immune response. Considerable efforts have been made to develop an HIV vaccine.
A cell infected with HIV virus has many distinct epitopes on its surface. Each epitope can be targeted by the cellular immune response mediated by T-lymphocytes. These T-lymphocytes become sensitized to specific epitopes by exposure to antigens brought to the T-cells by antigen presenting cells (e.g macrophages).
HIV vaccines have been developed to direct cellular immunity mechanisms toward a blood borne HIV virus by sensitizing T-cells, via antigen presenting cells (APCs) exposed to the vaccine, to suites of epitopes on the surface of cells infected with the virus.
Vectors used to introduce vaccines into the cellular immunity pathways have included adenovirus vectors. A problem with traditional vaccine approaches to treating patients already infected with HIV has been the fact that adenovirus vectors tend to activate CD4+ T-cells which in turn can potentially make pre-existing HIV infection more virulent. Another problem with HIV vaccine designs, in general, has been that the end result is to target large suites of epitopes on the surface of the cells infected with the virus, possibly targeting epitopes which could actually worsen various pathological aspects of the HIV infection.
Until recently, little was known about the specific effect of targeting specific epitopes on the surface of cells infected with the HIV virus. Each time a vaccine vector is given to a person with HIV disease, a number of epitopes are targeted, and a number of immune response parameters are measured. Associating a specific response with a specific epitope has been essentially impossible from an analysis of a single vaccine administration. Data from the administration of multiple vaccines to multiple sets of HIV infected subjects with corresponding cellular immune responses could, in theory, allow the effects of the individual epitopes to be de-convolved, essentially through a very computational intensive cross-correlation exercise.
Recent work in the field has brought modern super-computer technology to bear on this problem, resulting in a list of putative individual pathogen-relevant effects of individual epitopes on the surface of cells infected with the HIV virus.
Results from immunization with antigen-containing PLGA microspheres made from a double-emulsion process utilizing organic solvents have been mixed, however, perhaps owing to the fact that the solvent systems and shear forces used in such microsphere fabrication processes can cause protein conformational changes that may interfere with the antigen-presenting event.
Peptides injected into the lymphatic system can be taken up by APCs, thereby producing an immune response. If a single APC takes up more than one antigen and simultaneously presents multiple antigens to T-cells, this may result in a cellular immune response wherein the response is targeted to only one of the antigens that was presented.
Methods for relieving the effects of immunodominance are described in published US patent application 20080260780, entitled “Materials And Methods Relating To Improved Vaccination Strategies”; US patent application 20090269362, entitled “Method for Controlling Immunodominance”; and US patent application 20100119535, entitled “Compositions and Methods for Immunodominant Antigens.”